This application for a Midcareer Investigator Award in Patient-Oriented Research is submitted by Richard E. Chaisson, M.D, Professor of Medicine, Epidemiology and International Health at the Johns Hopkins University. The applicant completed subspecialty training in infectious diseases and clinical epidemiology in 1987. Since that time, he has built a successful and productive research program within the Johns Hopkins AIDS Service, a multidisciplinary clinical care enterprise for adults with HIV infection. In addition, he has organized and led the clinical and research efforts of the Baltimore City Health Department Tuberculosis Clinic, and has undertaken field trials in HIV-related tuberculosis in Haiti and South Africa. In 1998 Dr. Chaisson was promoted to Professor and began a refocusing of his academic activities and commitments. This application is intended to support this effort. Dr. Chaisson has relinquished the directorship of the AIDS Service and has appointed a replacement director of the Tuberculosis Clinic in order to devote his full attention to clinical research in tuberculosis and HIV infection. Dr. Chaisson has founded the Johns Hopkins University Center for Tuberculosis Research, an interdivisional, multidisciplinary program dedicated to improving global tuberculosis control through innovations in diagnosis, treatment and prevention. The centerpiece of this initiative is field trial comparing alternative tuberculosis control strategies in communities within high-incidence countries, funded under the US Agency for International Development's Infectious Disease Initiative. This trial will be conducted in several countries and will randomly assign communities to one of three tuberculosis control strategies: i) directly observed therapy (DOT) for active cases; ii) DOT plus screening of household contacts for active disease; and iii) DOT plus screening and preventive therapy for household contacts. This trial will provide important insight into effective strategies for global tuberculosis control. The applicant is also Principal Investigator of the Baltimore Tuberculosis Trials Consortium site, and a funded investigator in other studies of tuberculosis epidemiology and control. With support under this award, he will develop an integrate program in tuberculosis research utilizing the clinical and laboratory resources of the Baltimore Tuberculosis Clinic, the Johns Hopkins University and sites in developing countries with high tuberculosis incidence. Moreover, he will serve as mentor to junior faculty in infectious diseases and related fields who are beginning academic careers in patient-oriented research. A mentoring program organized to enhance professional development and independent scholarly activity will be undertaken with two recent faculty recruits. An award under this program will substantially enhance the research and mentoring capabilities of the applicant, and will contribute to the generation of new knowledge essential for the control of tuberculosis worldwide.